Hajer G. Ibrahim is a Clinical Psychiatric Pharmacist at Kaiser Permanente (KP) San Jose Medical Center, a Clinical Pharmacist at Kindred Hospital Baldwin Park in California, and an Adjunct Clinical Assistant Professor of Pharmacy Practice and Administration at Western University of Health Sciences, College of Pharmacy, in Pomona, California. Benjamin J. Malcolm is a Psychopharmacology Consultant at Spirit Pharmacist (Spiritpharmacist.com) and a former Assistant Professor of Pharmacy Practice and Administration at Western University of Health Sciences, College of Pharmacy. Hyma Gogineni is an Associate Professor of Pharmacy Practice and Administration at Western University of Health Sciences, College of Pharmacy, a Clinical Pharmacy Specialist (GI/Liver/Diabetes/Tobacco Treatment) at the Veterans Affairs Loma Linda Healthcare System Ambulatory Care Center, and and a Board of Pharmacy Specialist (BPS) Ambulatory Care Specialty Council in California. Correspondence: Hajer G. Ibrahim (hgibrahim@westernu.edu)
Author disclosures The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Ethics and consent This study has been deemed exempt by the VA Loma Linda Healthcare System institutional review board research team.
Background: Long-acting injectable antipsychotics (LAIAs) are integral for managing schizophrenia, schizoaffective disorder, and bipolar I disorder among veterans. Studies comparing LAIAs, such as risperidone microspheres and paliperidone palmitate, are limited. The primary objective of our study was to compare the number of psychiatric hospitalizations among veterans initiated on risperidone microspheres and those taking paliperidone palmitate pre- and post-LAIA initiation.
Methods: We included veterans who had received ≥ 2 injections of risperidone microspheres or paliperidone palmitate between January 1, 2016 and December 31, 2018. Nonadherence was defined as missing an injection by > 3 days for risperidone microspheres and > 7 days for paliperidone palmitate. Pre-LAIA and post-LAIA hospitalizations and rehospitalizations were assessed using a pre–post design with equivalent periods. Descriptive statistics were used for demographics and diagnoses. Nonparametric tests were used to analyze primary and secondary outcomes.
Results: The study included 97 veterans; 44 took risperidone microspheres and 53 received paliperidone palmitate. Participants’ average mean (SD) age was 46 (13.8) years, 92% were male, and 94% were diagnosed with schizophrenia or schizoaffective disorder. Veterans administered risperidone microspheres had fewer mean (SD) post-LAIA hospitalizations (0.4 [1.0] vs 0.9 [1.5]; P = .02), were less likely to be rehospitalized (22.7% vs 47.2%; P = .013) and had a shorter mean (SD) treatment duration (41.6 [40.2] vs 58.2 [45.7] weeks; P = .04) compared with paliperidone palmitate.
Conclusion: Veterans receiving risperidone microspheres had fewer posttreatment psychiatric hospitalizations and were less likely to be rehospitalized .
Medication nonadherence is common with oral antipsychotic formulations, resulting in relapse, increased morbidity, and more frequent psychiatric hospitalization.1-7 Psychiatric hospitalization and illness decompensation is costly to health care systems and leads to reduced quality of life for veterans and families.6,7 Long-acting injectable antipsychotics (LAIAs) were developed to enhance antipsychotic adherence and improve patient outcomes, including reduced psychiatric hospitalization.8-12
Little outcomes data exist comparing LAIAs, including biweekly risperidone microspheres and monthly paliperidone palmitate.10-13 Risperidone microspheres require a 3-week oral crossover and are administered every 2 weeks, whereas paliperidone palmitate does not require an oral crossover and is administered every 4 weeks. The paliperidone palmitate loading regimen replaces an oral crossover.
The primary objective of this study was to compare the number of psychiatric hospitalizations between veterans administered risperidone microspheres and those on paliperidone palmitate pre- and post-LAIA initiation. Secondary objectives were to assess rehospitalization rates between patients taking risperidone microspheres and paliperidone palmitate, reduction in pre- and posthospitalization rates with LAIAs, and medication adherence.
Methods
This observational study with a retrospective cohort design was conducted at the Veterans Affairs Loma Linda Healthcare System (VALLHS) in California. We examined veterans who were initiated on LAIAs risperidone microspheres or paliperidone palmitate from January 01, 2016 through December 31, 2018. Veterans who were aged ≥ 18 years and received ≥ 2 injections of either risperidone microspheres or paliperidone palmitate during the study period were included. Veterans were excluded if they had received < 2 doses of either LAIA, received the LAIA outside of the review period, were nonadherent to risperidone crossover if they received risperidone microspheres, or transferred their care to another facility. At VALLHS, LAIA injections are administered by a nurse, and veterans must travel to the facility to receive the injections.
Extracted patient chart elements included participant demographics; diagnoses; comorbid alcohol, nicotine, opioid, or other substance use; duration on LAIA; psychiatric hospitalizations pre- and postinitiation of the LAIA; medication adherence; and medication discontinuation based on clinician documentation and clinic orders (Table 1).
Nonadherence to LAIA was defined as missing an injection by > 3 days for risperidone microspheres and > 7 days for paliperidone palmitate. This time frame was based on pharmacokinetic information listed in the products’ package inserts.14,15 Nonadherence to oral risperidone crossover with risperidone microspheres was defined as ≤ 80% of days covered.
Data Analysis
Patient demographics were analyzed using descriptive statistics and experimental comparisons between the risperidone microspheres and paliperidone palmitate groups to assess baseline differences between groups. Psychiatric hospitalizations pre- and post-LAIA were analyzed with parallel group (between veterans–independent groups) and pre-post (within veterans–dependent groups) designs. Index hospitalizations were examined for a period equivalent to the length of time veterans were on the LAIA. Psychiatric rehospitalization rates were analyzed for patients who had index hospitalizations and were rehospitalized for any period when they were receiving the LAIA. Incidences of pre- and post-LAIA hospitalizations were calculated in 100 person-years.
Parallel-group analysis was analyzed using the χ2 and Mann-Whitney U tests. Pre-post analyses were analyzed using the Wilcoxon rank sum test. P was set at < .05 for statistical significance.
